Chen, X;
Wu, Y;
Diao, Z;
Han, X;
Li, D;
Ruan, X;
Liu, W;
(2019)
C1q/tumor necrosis factor‐related protein‐3 improves renal fibrosis via inhibiting notch signaling pathways.
Journal of Cellular Physiology
, 234
(12)
pp. 22352-22364.
10.1002/jcp.28801.
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Abstract
C1q/tumor necrosis factor-related protein-3 (CTRP3) has been extensively reported as an important role involved in antifibrosis, antiapoptosis, and anti-inflammation. However, the role of CTRP3 involved in renal fibrosis remains unclear. Our current study explored the role of CTRP3 in renal fibrosis and its underlying mechanisms by using serums and renal biopsy specimens from renal fibrosis patients and control subjects, rats models with the surgery of unilateral ureteral obstruction (UUO) and human renal proximal tubular epithelial cells (HRPTEpiCs). We found that circulating levels of CTRP3 had no significant difference between renal fibrosis patients and healthy subjects; however, renal CTRP3 expression was markedly downregulated in the fibrotic region with an abundant expression of collagen-I. In UUO rat models, circulating levels of CTRP3 have not changed with the prolonged obstruction of the kidney; renal CTRP3 expression was decreased with the severity of renal fibrosis; adenovirus-mediated CTRP3 treatment inhibited renal interstitial fibrosis. In vitro experiments revealed that CTRP3 attenuates TGF-β1 induced tubular epithelial cells fibrotic changes; CTRP3 knockdown facilitates the expression of fibrotic markers in TGF-β1-induced HRPTEpiCs; recombinant CTRP3 or adenovirus-mediated CTRP3 overexpression significantly inhibited the Notch signaling pathway-associated factors, and knockdown of CTRP3 increased TGF-β1-mediated activation of the Notch signaling pathways. Collectively, our current study found that CTRP3 could improve renal fibrosis, to some extent, through inhibiting the Notch pathway.
| Type: | Article |
|---|---|
| Title: | C1q/tumor necrosis factor‐related protein‐3 improves renal fibrosis via inhibiting notch signaling pathways |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/jcp.28801 |
| Publisher version: | https://doi.org/10.1002/jcp.28801 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | C1q/tumor necrosis factor-related protein-3 (CTRP3), Notch signaling pathway, TGF-β1, renal interstitial fibrosis, tubular epithelial cells |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10090356 |
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